A principal aim of the proposed research is to extend and refine studies on the interaction between ionizing radiation and transposon mobility in induction of germ line genetic damage in Drosophila. This interaction will be tested by induction of P element transposition in hybrids. Traits induced by hybrid dysgenesis, namely high mutability, sterility, chromosome loss, transmission distortion, and translocations will be used as endpoints to test any synergism that may result from the combined effect of X-irradiation and P element mobility during specific stages of gametogenesis. The observed synergism for X- ray- and P element-induced dominant lethals and sterility will be measured at various X-ray doses. Dominant lethals will also be tested in DNA repair-deficient mutants. The effect of X rays on the reversion rate of visible P element insertion mutations in a multiply marked X chromosome will be studied. Increasing evidence implicates genetic transposition and chromosomal rearrangements in the genetic basis of carcinogenesis Transposable elements have a genomic organization similar to that of retroviruses. A component of X- ray-induced genetic damage, namely chromosome breaks and rearrangements are events that are also frequently associated with P element transposition. The study of the interaction between X rays, a known oncogenic agent, and transposon mobility in Drosophila provides an important model system. A second goal is the cloning of one or more of eleven X-linked DNA repair genes via P element insertion mutagenesis, and selection for MMS sensitivity in grandsons of F2 dysgenic females. In situ hybridization and complementation analysis will confirm the nature of the mutation. Cloning of these repair genes should provide insight on their organization, mutation and transcription.
